Liposomal Bupivacaine With or Without Hydromorphone for the Improvement of Pain Control After Laparotomy in Patients With Gynecological Malignancies

Wound Infiltration With Liposomal Bupivacaine With or Without Intrathecal Analgesia in Laparotomy for Gynecological Malignancy: A Randomized Controlled Trial

This phase IV trial studies how well liposomal bupivacaine with or without hydromorphone works in improving pain control during the first 24 hours after surgery in patients with gynecological malignancies undergoing laparotomy. Liposomal bupivacaine is routinely infiltrated into the skin surrounding the abdominal incision, and is effective in providing good relief of incisional pain. Hydromorphone is also a type of pain medication that may provide better management of deep abdominal pain. It is not yet known if giving liposomal bupivacaine with or without hydromorphone will work better in improving pain in patients with gynecological malignancies during the first 24 hours after surgery.

Study Overview

• Status: Completed
• Conditions: Malignant Female Reproductive System Neoplasm
• Intervention / Treatment: Other: Questionnaire Administration; Procedure: Laparotomy; Drug: Liposomal Bupivacaine; Drug: Hydromorphone

Detailed Description

PRIMARY OBJECTIVES:

I. Evaluate if no additional intervention is noninferior to intrathecal analgesia (ITA) for postoperative pain experience 24 hours after surgery after laparotomy for gynecological malignancy within an established enhanced recovery pathway which includes incisional liposomal bupivacaine (ILB).

II. Evaluate the effect of intrathecal analgesia on patient satisfaction with postoperative analgesia after laparotomy for gynecological malignancy.

III. Report the impact of ITA use on cost. IV. Validate the Quality of Recovery (QOR)-15 in our population.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients undergo standard of care laparotomy and then receive liposomal bupivacaine.

ARM II: Patients undergo standard of care laparotomy and then receive liposomal bupivacaine and hydromorphone intrathecally (IT).

• Study Type: Interventional
• Enrollment (Actual): 105
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Elective surgery for suspected (based on consulting surgeon's opinion-imaging, laboratory [lab], pathology [path]) gynecological malignancy, enhanced recovery after surgery (ERAS) protocol

Exclusion Criteria:

• Inability to read or understand English
• Prehospitalization narcotic use if weekly average daily oral morphine equivalent of > 20 mg
• Chronic pain syndromes such as fibromyalgia
• Extensive surgery planned (surrogate for post-operative [postop] pain): Planned intensive care unit (ICU) admission, abdominoperineal resection, exenteration, use of intraoperative radiation (IORT), hyperthermic intraperitoneal chemotherapy (HIPEC)

• Contraindication to neuraxial analgesia:

  • Coagulopathy

    • International normalized ratio (INR) > 1.2 current or predicted after surgery (e.g. planned right hepatic resection)
    • Thrombocytopenia. Platelets (plts) < 100
    • Hemophiliac disease states (hemophilia, von Willebrand disease, etc.)
    • Patients receiving antithrombotic or thrombolytic therapy are excluded according to the American Society of Regional Anesthesia and Pain Medicine (ASRA) guidelines
  • Localized infection at the potential site of injection
  • Significant developmental or structural spinal abnormalities that would preclude a safe spinal technique. These include spina bifida, tethered spinal cord, lumbar spinal fusion, and active lumbar radiculopathy
• Patients with stage 4 or 5 kidney disease (glomerular filtration rate [GFR] less than 30 ml/min per 1.73 m^2)
• Intolerance or allergy to opioids, acetaminophen, or amide-type local anesthetics
• Current pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm I (laparotomy, liposomal bupivacaine); Patients undergo standard of care laparotomy and then receive liposomal bupivacaine.	Other: Questionnaire Administration; Ancillary studies; Procedure: Laparotomy; Undergo laparotomy; Drug: Liposomal Bupivacaine; Drug; Other Names: Exparel; Bupivacaine Liposome Injectable Suspension
Experimental: Arm II (laparotomy, liposomal bupivacaine, hydromorphone); Patients undergo standard of care laparotomy and then receive liposomal bupivacaine and hydromorphone IT.	Other: Questionnaire Administration; Ancillary studies; Procedure: Laparotomy; Undergo laparotomy; Drug: Liposomal Bupivacaine; Drug; Other Names: Exparel; Bupivacaine Liposome Injectable Suspension; Drug: Hydromorphone; Given IT; Other Names: (-)-Hydromorphone; Dihydromorphinone; Hydromorphon

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Benefit of Analgesia Score (OBAS)	The Overall Benefit of Analgesia Score (OBAS) is a multi-dimensional survey that measures a patient's benefit from postoperative pain therapy. It assesses pain intensity, opioid-related adverse events, and patient satisfaction with analgesia. Each of 7 questions are scored on a scale from 0 to 4 where 0=minimal/not at all and 4=maximum/very much. The total score is a sum of the 7 item scores with question 7 scored as 4 minus the patient reported number. Total scores range from 0 to 28 with lower scores representing greater benefit from analgesic therapy. The median total OBAS score for each group is presented.	Up to 24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative 24-hour Narcotic Consumption	Various narcotic medications are standardized and reported as Morphine Milligram Equivalents (MME).	Up to 24 hours after surgery
Post-operative Pain Scores	Postoperative pain is scored on a scale of 0 - 10, with the lower score showing a better outcome.	Up to 24 hours after surgery
Time to First Analgesic Request	Amount of time from leaving surgery to the first request for pain relief.	Up to 24 hours after surgery
Use of Intravenous (IV) Patient-controlled Analgesia	Number of patients that used IV, patient controlled analgesia after surgery.	Up to 24 hours after surgery
Use of Intravenous Rescue Opioids	Number of patients that needed IV rescue opioids after surgery.	Up to 24 hours after surgery
Length of Stay	Length of associated hospitalization in days.	Up to 1 week after surgery
Additional Fluid Requirement After 24 Hours of Surgery	Number of patients requiring additional IV fluids after surgery.	Up to 24 hours after surgery
Weight Gain Following Surgery	Weight difference post- and pre-surgery.	Up to 24 hours after surgery
Total Cost of Care	All medical costs occurring during hospitalization.	Entire hospitalization, approximately 2-5 days
Incidence of Adverse Events	Reported as the number participants reporting one or more adverse events on each study arm.	Up to 24 hours after surgery
Operating Room Time	Length of time from when the patient entered the operating room to when they left.	Approximately 8 hours
Surgical Time	Time from first incision to surgical site closure.	Approximately 8 hours
Pain Management	Pharmaceutical costs associated with pain management.	Whole hospitalization, approximately 2-5 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Recovery-15 (QoR-15) Total Score	The Quality of Recovery (QoR-15) questionnaire is a 15-item survey that patients rate to measure the quality of their recovery after surgery. Each item in the questionnaire is graded on an 11-point numeric rating scale with total scores ranging from 15 to 150. Higher scores indicate better recovery.	At 24 hours after surgery

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Sean C Dowdy, Mayo Clinic

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2020
• Primary Completion (Actual): August 8, 2023
• Study Completion (Actual): August 8, 2023

Study Registration Dates

• First Submitted: February 4, 2020
• First Submitted That Met QC Criteria: February 4, 2020
• First Posted (Actual): February 6, 2020

Study Record Updates

• Last Update Posted (Actual): October 16, 2024
• Last Update Submitted That Met QC Criteria: October 14, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics; Analgesics, Opioid; Narcotics; Anesthetics, Local; Bupivacaine; Hydromorphone
• Other Study ID Numbers: MC2061 (Other Identifier: Mayo Clinic in Rochester); NCI-2020-00609 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 19-010500 (Other Identifier: Mayo Clinic Institutional Review Board)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No